Systematic Review and Meta-analysis of Indirect Protection Afforded by Vaccinating Children Against Seasonal Influenza: Implications for Policy

Background. Universal childhood vaccination is a potential solution to reduce seasonal influenza burden. Methods. We reviewed systematically the literature on "herd"/indirect protection from vaccinating children aged 6 months to 17 years against influenza. Results. Of 30 studies included, 14 (including 1 cluster randomized controlled trial [cRCT]) used live attenuated influenza vaccine, 11 (7 cRCTs) used inactivated influenza vaccine, and 5 (1 cRCT) compared both vaccine types. Twenty of 30 studies reported statistically significant indirect protection effectiveness (IPE) with point estimates ranging from 4% to 66%. Meta-regression suggests that studies with high quality and/or sufficiently large sample size are more likely to report significant IPE. In meta-analyses of 6 cRCTs with full randomization (rated as moderate quality overall), significant IPE was found in 1 cRCT in closely connected communities where school-aged children were vaccinated: 60% (95% confidence interval [CI], 41%-72%; I-2 = 0%; N = 2326) against laboratory-confirmed influenza, and 3 household cRCTs in which preschool-aged children were vaccinated: 22% (95% CI, 1%-38%; I2 = 0%; N = 1903) against acute respiratory infections or influenza-like illness. Significant IPE was also reported in a large-scale cRCT (N = 8510) that was not fully randomized, and 3 ecological studies (N > 10 000) of moderate quality including 36% reduction in influenza-related mortality among the elderly in a Japanese school-based program. Data on IPE in other settings are heterogeneous and lacked power to draw a firm conclusion. Conclusions. The available evidence suggests that influenza vaccination of children confers indirect protection in some but not all settings. Robust, large-scaled studies are required to better quantify the indirect protection from vaccinating children for different settings/endpoints.